The primary goal of the project is to determine the mechanisms of action of several of the most extensively used antituberculosis drugs, including isoniazid, rifampin, ethionamide, ethambutol, and pyrazinamide. The methods by which mycobacteria develop drug resistance are also pertinent to the project. Experiments are also planned to investigate the antimycobacterial effects of drug combinations with the goal of finding drug regimens which are synergistic in relationship. The methods of study usually include measurements of drug effects on the incorporation of specific metabolic precursors into essential cellular components in Mycobacterium bovis strain BCG, avirulent strains of Mycobacterium tuberculosis or various atypical mycobacteria.